Clay County is a county in the U.S. state of South Dakota. As of the 2020 census, the population was 14,967. The county seat is Vermillion, which is also home to the University of South Dakota. The county is named for Henry Clay, American statesman, US Senator from Kentucky, and United States Secretary of State in the 19th century.

Vermillion is a city and the county seat of Clay County. It is in the southeastern corner of South Dakota, United States, and is the state's 12th-most populous city. According to the 2020 Census, the population was 11,695. The city lies atop a bluff near the Missouri River.